Progressive tissue fibrosis is a major cause of morbidity and mortality. Tissue fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process, which is different from the formation of fibrous tissue as a normal constituent of an organ or tissue. Scarring is confluent fibrosis that obliterates the architecture of the underlying organ or tissue. Pulmonary fibrosis is the formation or development of excess fibrous connective tissue in the lungs. Idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by progressive and unremitting matrix deposition in the interstitium of the lung. The clinical course of IPF is unrelenting and has characteristics reminiscent of cancer. IPF patients suffer from the inexorable accumulation of extracellular matrix in the gas-exchanging regions of the lung. One feature of IPF is the formation of fibroblastic foci, which are structures of accumulated myofibroblasts in the interstitium of the lung juxtaposed to the alveolar epithelium and are associated with destruction of the adjoining alveolar basement membrane.
Hyaluronan (HA) is a non-sulfated glycosaminoglycan produced by mesenchymal cells as well as a variety of tumor cells. CD44 is a cell surface receptor for HA and plays a role in inflammatory cell recruitment and activation, as well as tumor growth and metastasis.
While numerous mediators have been identified as initiating tissue fibrosis, the mechanisms that contribute to persistent fibrodestructive disease remain incompletely understood.